Anti-tmprss6 antibodies and uses thereof

Abstract

Provided herein are monoclonal antibodies that bind to the transmembrane serine protease 6 (TMPRSS6) protein, and methods of use thereof. In various embodiments of the disclosure, the antibodies are fully human antibodies that bind to TMPRSS6. In some embodiments, the antibodies disclosed herein are useful in a method for treating or preventing a disease, disorder or condition associated with TMPRSS6 in humans.

1 - 61 . (canceled) 
     
     
         62 . An isolated antibody or antigen-binding fragment thereof that binds to Transmembrane Protease Serine 6 (TMPRSS6) protein,
 wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (HCDRs) and three light chain complementarity determining regions (LCDRs),   wherein the three HCDRs and the three LCDRs comprise one of the following sets of complementarity determining regions:   (a) SEQ ID NO: 4 (HCDR1), SEQ ID NO:6 (HCDR2), SEQ ID NO:8 (HCDR3), SEQ ID NO:12 (LCDR1), SEQ ID NO:14 (LCDR2), and SEQ ID NO:16 (LCDR3);   (b) SEQ ID NO: 24 (HCDR1), SEQ ID NO:26 (HCDR2), SEQ ID NO:28 (HCDR3), SEQ ID NO:12 (LCDR1), SEQ ID NO:14 (LCDR2), and SEQ ID NO:16 (LCDR3);   (c) SEQ ID NO: 34 (HCDR1), SEQ ID NO:36 (HCDR2), SEQ ID NO:38 (HCDR3), SEQ ID NO:12 (LCDR1), SEQ ID NO:14 (LCDR2), and SEQ ID NO:16 (LCDR3);   (d) SEQ ID NO: 44 (HCDR1), SEQ ID NO:46 (HCDR2), SEQ ID NO:48 (HCDR3), SEQ ID NO:52 (LCDR1), SEQ ID NO:54 (LCDR2), and SEQ ID NO:56 (LCDR3);   (e) SEQ ID NO: 64 (HCDR1), SEQ ID NO:66 (HCDR2), SEQ ID NO:68 (HCDR3), SEQ ID NO:72 (LCDR1), SEQ ID NO:74 (LCDR2), and SEQ ID NO:76 (LCDR3);   (f) SEQ ID NO: 84 (HCDR1), SEQ ID NO:86 (HCDR2), SEQ ID NO:88 (HCDR3), SEQ ID NO:92 (LCDR1), SEQ ID NO:14 (LCDR2), and SEQ ID NO:94 (LCDR3);   or   (g) SEQ ID NO: 102 (HCDR1), SEQ ID NO:104 (HCDR2), SEQ ID NO: 106 (HCDR3), SEQ ID NO:110 (LCDR1), SEQ ID NO:14 (LCDR2), and SEQ ID NO:112 (LCDR3).   
     
     
         63 . The antibody or antigen-binding fragment thereof of  claim 62 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR)/a light chain variable region (LCVR) comprising one of the following amino acid sequence pairs:
 (a) SEQ ID NOs: 2/10;   (b) SEQ ID NOs: 22/10;   (c) SEQ ID NOs: 32/10;   (d) SEQ ID NOs: 42/50;   (e) SEQ ID NOs: 62/70;   (f) SEQ ID NOs: 82/90; or   (g) SEQ ID NOs: 100/108.   
     
     
         64 . The antibody or antigen-binding fragment thereof of  claim 62 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain (HC)/light chain (LC) comprising one of the following amino acid sequence pairs:
 (a) SEQ ID NOs: 18/20;   (b) SEQ ID NOs: 30/20;   (c) SEQ ID NOs: 40/20;   (d) SEQ ID NOs: 58/60;   (e) SEQ ID NOs: 78/80;   (f) SEQ ID NOs: 96/98; or   (g) SEQ ID NOs: 114/116.   
     
     
         65 . An isolated antibody or antigen-binding fragment thereof that binds to Transmembrane Protease Serine 6 (TMPRSS6) protein,
 wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (HCDRs) and three light chain complementarity determining regions (LCDRs),   wherein the three HCDRs comprise the amino acid sequences of SEQ ID NO: 102 (HCDR1), SEQ ID NO:104 (HCDR2), and SEQ ID NO:106 (HCDR3), and the three LCDRs comprise the amino acid sequences of SEQ ID NO:110 (LCDR1), SEQ ID NO:14 (LCDR2), and SEQ ID NO:112 (LCDR3).   
     
     
         66 . The antibody or antigen-binding fragment thereof of  claim 65 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO:100 and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 108. 
     
     
         67 . The antibody or antigen-binding fragment thereof of  claim 66 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 114 and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 116. 
     
     
         68 . A pharmaceutical composition comprising the isolated antibody or antigen-binding fragment thereof of  claim 65  and a pharmaceutically acceptable carrier or diluent. 
     
     
         69 . A polynucleotide molecule comprising a polynucleotide sequence that encodes the antibody or antigen-binding fragment thereof of  claim 65 . 
     
     
         70 . A host cell comprising the polynucleotide molecule of  claim 69 . 
     
     
         71 . A method of producing an isolated antibody or antigen-binding fragment thereof that binds to Transmembrane Protease Serine 6 (TMPRSS6), comprising:
 culturing the host cell of claim  70  under conditions permitting production of the antibody or antigen-binding fragment thereof, and   recovering the antibody or antigen-binding fragment thereof so produced.   
     
     
         72 . The method of  claim 71 , further comprising formulating the antibody or antigen-binding fragment thereof as a pharmaceutical composition comprising the antibody or antigen-binding fragment thereof and a pharmaceutically acceptable carrier. 
     
     
         73 . A method of ameliorating at least one symptom or indication of a disease or disorder associated with iron overload, the method comprising administering a pharmaceutical composition comprising a therapeutically effective amount of the antibody or antigen-binding fragment thereof of  claim 65  to a subject in need thereof. 
     
     
         74 . The method of  claim 73 , wherein disease or disorder is a congenital dyserythropoietic anemia, Diamond-Blackfan anemia, alpha thalassemia, beta thalassemia, a transfusion-dependent hemolytic anemia, myelodysplastic syndrome, sickle cell disease, polycythemia vera, hereditary hemochromatosis, or chronic liver disease. 
     
     
         75 . The method of  claim 74 , wherein the disease or disorder is beta thalassemia.